(2'Z-3'E)-6-bromoindirubin-3'-(O-{2-[4-(2-methoxyethyl)piperazin-1-yl]ethyl}oxime) | 1067884-48-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2'Z-3'E)-6-bromoindirubin-3'-(O-{2-[4-(2-methoxyethyl)piperazin-1-yl]ethyl}oxime)
• CAS: 1067884-48-3
• 化学式: C₂₅H₂₈BrN₅O₃
• 分子量: 526.433
• InChiKey: HUDVRTTVWXVPMO-HLDOLBPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  34.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78.43
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  1-(2-甲氧基乙基)哌嗪 、 (2′Z-3′E)-6-bromoindirubin-3′-[O-(2-bromoethyl)oxime] 以 N,N-二甲基甲酰胺 为溶剂， 以100%的产率得到(2'Z-3'E)-6-bromoindirubin-3'-(O-{2-[4-(2-methoxyethyl)piperazin-1-yl]ethyl}oxime)
  参考文献：
  名称：

  Soluble 3′,6-Substituted Indirubins with Enhanced Selectivity toward Glycogen Synthase Kinase -3 Alter Circadian Period

  摘要：

  Glycogen synthase kinase -3 (GSK-3) is a key enzyme involved in numerous physiological events and in major diseases, such as Alzheimer's disease, diabetes, and cardiac hypertrophy. Indirubins are bis-indoles that can be generated from various natural sources or chemically synthesized. While rather potent and selective as GSK-3 inhibitors, most indirubins exhibit low water solubility. To address the issue of solubility, we have designed novel analogues of 6-bromo-indirubin-3'-oxime with increased hydrophilicity based on the GSK-3/indirubins cocrystal structures. The new derivatives with an extended amino side chain attached at position 3' showed potent GSK-3 inhibitory activity, enhanced selectivity, and dramatically increased water solubility. Furthermore, some of them displayed little or no cytotoxicity. The new indirubins inhibit GSK-3 in a cellular reporter model. They alter the circadian period measured in rhythmically expressing cell cultures, suggesting that they might constitute tools to investigate circadian rhythm regulation.

  DOI：

  10.1021/jm800648y

文献信息

• Soluble 3′,6-Substituted Indirubins with Enhanced Selectivity toward Glycogen Synthase Kinase -3 Alter Circadian Period
  作者：Konstantina Vougogiannopoulou、Yoan Ferandin、Karima Bettayeb、Vassilios Myrianthopoulos、Olivier Lozach、Yunzhen Fan、Carl Hirschie Johnson、Prokopios Magiatis、Alexios-Leandros Skaltsounis、Emmanuel Mikros、Laurent Meijer

  DOI：10.1021/jm800648y

  日期：2008.10.23

  Glycogen synthase kinase -3 (GSK-3) is a key enzyme involved in numerous physiological events and in major diseases, such as Alzheimer's disease, diabetes, and cardiac hypertrophy. Indirubins are bis-indoles that can be generated from various natural sources or chemically synthesized. While rather potent and selective as GSK-3 inhibitors, most indirubins exhibit low water solubility. To address the issue of solubility, we have designed novel analogues of 6-bromo-indirubin-3'-oxime with increased hydrophilicity based on the GSK-3/indirubins cocrystal structures. The new derivatives with an extended amino side chain attached at position 3' showed potent GSK-3 inhibitory activity, enhanced selectivity, and dramatically increased water solubility. Furthermore, some of them displayed little or no cytotoxicity. The new indirubins inhibit GSK-3 in a cellular reporter model. They alter the circadian period measured in rhythmically expressing cell cultures, suggesting that they might constitute tools to investigate circadian rhythm regulation.